Higher risk of mortality in HIV-HBV co-infected patients from sub-Saharan Africa is observed at lower CD4 cell counts.

BACKGROUND

Hepatitis B virus (HBV) co-infection in human immunodeficiency virus (HIV)-positive individuals increases the risk of overall mortality, especially when HBV DNA levels are high. The role of CD4 cell counts in this association is poorly defined. We aimed to determine whether HIV-HBV co-infection influences changes in CD4 cell count before and during antiretroviral therapy and whether it affects mortality risk at levels of CD4.

METHODS

2052 HIV-positive participants from Côte d'Ivoire in a randomized-control trial assessing early or deferred ART were included. HBV-status was determined by hepatitis B surface antigen (HBsAg). Changes in CD4 cell levels were estimated using a mixed-effect linear model. The incidence rates of all-cause mortality were estimated at CD4 counts ≤350, 351-500, >500/mm and were compared between HBV-status groups as incidence rate ratios (IRR).

RESULTS

At baseline, 190 (9%) were HBsAg-positive [135 (71%) with HBV DNA <2000 IU/mL, 55 (29%) ≥2000 IU/mL]. Follow-up was a median 58 months (IQR = 40-69). Between co-infection groups, there were no differences in CD4 decline before ART initiation and no differences in CD4 increase after ART initiation. After adjusting for sex, age, baseline HIV RNA level, and early/deferred ART arm, mortality rates were not significantly different between HBsAg-positive versus HBsAg-negative participants across strata of CD4 levels. However, HBsAg-positive individuals with HBV-DNA ≥2000 IU/mL versus HBsAg-negative individuals had increased mortality rates at ≤350/mm (adjusted-IRR = 3.82, 95% CI = 1.11-9.70) and 351-500/mm (adjusted-IRR = 4.37, 95% CI = 0.98-13.02), but not >500/mm (adjusted-IRR = 1.07, 95% CI = 0.01-4.91).

CONCLUSION

Despite no effect of HBV-infection on CD4 levels, HIV-HBV co-infected individuals with high HBV replication are at higher risk of mortality when CD4 is <500/mm.